Exploring effects of melatonin supplementation on insulin resistance: An updated systematic review of animal and human studies.

BACKGROUND: Insulin resistance (IR), defined as an impaired response to insulin stimulation of target tissues, is a substantial determinant of many metabolic disorders. This study aimed to update the findings of the previous systematic review evidence regarding the effect of melatonin on factors related to IR, including hyperinsulinemia, hyperglycemia, homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI). METHODS: We systematically reviewed the evidence on the impact of melatonin supplementation on IR indices, fasting insulin, and fasting plasma glucose. PubMed, ScienceDirect, SCOPUS, and Google Scholar databases were searched until March 2024. RESULTS: We identified 6114 potentially relevant articles during the search. Eighteen animal studies and 15 randomized clinical trials met the inclusion criteria. The results indicated that melatonin supplementation reduced fasting plasma glucose (FPG, 14 out of 29 studies), fasting insulin (22 out of 28 studies), HOMA-IR (28 out of 33 studies), and increased QUICKI (7 out of 7 studies). According to RCT studies, melatonin treatment at a dosage of 10 mg reduced HOMA-IR levels in individuals with various health conditions. CONCLUSION: According to most evidence, melatonin supplementation may decrease fasting insulin and HOMA-IR and increase QUICKI but may not affect FPG.

Efficacy of Glucagon-like Peptide-1 Receptor Agonists in Overweight/Obese and/or T2DM Adolescents: A Meta-analysis Based on Randomized Controlled Trials.

Objective: This meta-analysis aimed to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in overweight/obese and/or type 2 diabetes mellitus (T2DM) adolescents aged <18 years. Methods: Herein, we searched PubMed, Embase, Web of Science, and Cochrane Library for all randomized controlled trials (RCTs) comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data up to August 2023 for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, P<0.001) than the control group. However, there was no difference in fasting blood glucose (FPG; RD=-2.07mg/dL, P=0.065) between the two groups. Nonetheless, the experimental group that administered exenatide showed a no significant reduction in HbA1c (P=0.253) and FPG (P=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28kg, P=0.002) and BMI (RD=-1.63kg/m2, P=0.002) compared to the control group. The experimental group was adopted with liraglutide (RD=-2.31kg, P=0.038) or exenatide (RD=-2.70kg, P<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. But for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81kg/m2, P=0.260). For the experimental group that was adopted with exenatide, BMI revealed a more significant decline in the intervention group than in the control group (RD=-1.14kg/m2, P<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide is better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide is better than liraglutide.

Retrospective Observational Study on Assessing Sitagliptin and Dapagliflozin as a Fixed-Dose Combination in the Indian Population With Type 2 Diabetes Mellitus: The SIDAXA Study.

Introduction Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, necessitates multifaceted treatment approaches. Emerging studies highlight the cardiovascular advantages of sodium-glucose transport protein 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors in T2DM. This investigation delves into the synergistic effects of the fixed-dose combination (FDC) of sitagliptin and dapagliflozin, offering insights into its safety and efficacy for the Indian population. Methods This real-world, retrospective, observational study spanned 328 cases across 111 Indian centres, evaluating the safety, efficacy, and clinical utilization of the sitagliptin and dapagliflozin FDC in T2DM patients after obtaining ethical approval. Assessments at baseline, week four, and week 12 encompassed hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), postprandial blood glucose (PPBG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight change. The statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 29.0.1.0(171) (IBM Corp., Armonk, NY, USA) with a significance level p<0.05. Results Study participants [mean age: 51.14±5.55 years, 77.74% (n=255) males, 22.26% (n=73) females] exhibited prevalent risk factors like sedentary lifestyle (n=167, 50.91%) and smoking (n=147, 44.82%). Comorbidities included hypertension (n=235, 71.65%) and dyslipidaemia (n=139, 42.38%). Metformin (n=282, 85.98%) and sulfonylurea (n=134, 40.85%) were commonly prescribed concomitant oral antidiabetic agents (OADs). FDC administration significantly reduced HbA1c by 1.05 ± 0.83% (p < 0.0001) at week 12. FPG and PPBG showed significant reductions of 22.98 ± 22.23 mg/dL (p < 0.0001), 165.50 ± 37.02 mg/dL and 40.94 ± 36.04 mg/dL (p < 0.0001) at four weeks respectively. By week 12, significant reductions were noted in SBP (14.61±13.98mmHg reduction, p-value <0.0001), DBP (7.80±8.45mmHg reduction, p-value <0.0001), and LDL-C levels (18.14±23.95 mg/dL reduction, p-value <0.0001). In patients with established cardiovascular disease, there was reduction in HbA1c levels by 1.02 ± 0.63% after 12 weeks, with FPG decreasing by 54.52 ± 32.67 mg/dL and PPBG decreasing by 88.73 ± 44.90 mg/dL. Treatment-emergent adverse events included headache, changes in micturition, genital mycotic infection, and nausea and diarrhoea which were mild, transient, and necessitated no treatment discontinuation. Conclusion The FDC of sitagliptin and dapagliflozin significantly improved glycaemic control and lipid profiles in T2DM patients, particularly those with coronary artery disease. It demonstrated a favourable safety profile in the Indian population, signifying its potential as an effective and well-tolerated therapeutic option in patients with established cardiovascular disease.

Non-linear associations of serum spermidine with type 2 diabetes mellitus and fasting plasma glucose: a cross-sectional study.

Background: Previous animal experiments have demonstrated the potential of spermidine to mitigate glucose intolerance, insulin resistance, and hyperinsulinemia. However, there remains a scarcity of epidemiological evidence supporting these findings. Therefore, we aimed to elucidate the associations of serum spermidine with T2DM and FPG. Materials and methods: The cross-sectional study was conducted from June to August 2019 in the rural areas of Fuxin County, Liaoning Province, China. A total of 4,437 participants were included in the study. The serum spermidine was detected using high-performance liquid chromatography with a fluorescence detector. FPG was measured using the hexokinase method. T2DM was defined as participants with a FPG level of 7.0 mmol/L or greater, or self-reported diagnosis of diabetes by a doctor. Restricted cubic spline model and piecewise linear regression model were used to explore the associations of serum spermidine with T2DM and FPG, respectively. Results: The mean (SD) age of the participants was 59.3 (10.0) years, with 622 out of 4,437 participants being defined as T2DM. The serum spermidine in participants stratified by age and BMI categories was significantly different, with p values of 0.006 and 0.001, respectively. Among all the participants, the association of serum spermidine with T2DM was J-shaped. The log (spermidine) was negatively associated with T2DM (OR = 0.68, 95% CI: 0.52 to 0.92, p = 0.01) below the inflection point, while log (spermidine) was not significantly associated with T2DM (OR = 1.97, 95% CI: 0.93 to 4.15, p = 0.07) above the inflection point. Among the participants without T2DM, the association of serum spermidine with FPG was inverted J-shaped. The log (spermidine) was positively associated with FPG (ß = 0.13, 95% CI: 0.05 to 0.21, p = 0.001) below the inflection point, while log (spermidine) was negatively associated with FPG (ß = -0.29, 95% CI: -0.42 to -0.16, p < 0.001) above the inflection point. Conclusion: In conclusion, non-linear associations of serum spermidine with T2DM and FPG were found in the cross-sectional study in Chinese rural adults. This provided insights into the use of spermidine for the prevention of T2DM, highlighting the potential role in public health prevention strategies of spermidine.

Association between depressive symptoms and prediabetes: NHANES 2007-2016 findings.

INTRODUCTION: The association between diabetes and depressive symptoms is well recognized. However, the impact of depressive symptoms on prediabetes remains unclear. This study aims to explore the specific correlation between depressive symptoms and prediabetes. METHODS: A total of 7467 participants from the National Health and Nutrition Examination Survey (NHANES) were included in this study, spanning five rounds of surveys conducted between 2007 and 2016. Weighted logistic regression was utilized to assess the relationship between depressive symptoms and prediabetes. RESULTS: Compared with the normoglycemic population, individuals with prediabetes had a significantly higher probability of experiencing trouble sleeping (P = 0.020). After adjusting for non-glucose factors, there was no significant correlation between PHQ-9 and prediabetes; however, severe depressive symptoms were positively associated with abnormal fasting plasma glucose (FPG) levels (OR = 1.093 [95 % CI 1.002, 1.192]). There was a positive correlation between trouble concentrating and FPG abnormalities (OR = 1.065 [95 % CI 1.004, 1.129]). LIMITATIONS: The cross-sectional design limits causal inference. CONCLUSION: Individuals with depressive symptoms, especially severe cases, should be targeted for prediabetes prevention and management efforts. The diverse symptom presentations may have distinct impacts on glucose, necessitating personalized prevention and management strategies.

Mediation effect of serum zinc on insulin secretion inhibited by methyl tert-butyl ether in gas station workers.

Methyl tert-butyl ether (MTBE), a type of gasoline additive, has been found to affect insulin function and glucose homeostasis in animal experiments, but there is still no epidemiological evidence. Zinc (Zn) is a key regulatory element of insulin secretion and function, and Zn homeostasis can be disrupted by MTBE exposure through inducing oxidative stress. Therefore, we suspected that Zn might be involved and play an important role in the process of insulin secretion inhibited by MTBE exposure. In this study, we recruited 201 male subjects including occupational and non-occupational MTBE exposure from Anhui Province, China in 2019. Serum insulin and functional analog fibroblast growth factor 1 (FGF1) and blood MTBE were detected by Elisa and headspace solid-phase microextraction and gas chromatography-high-resolution mass spectrometry. According to MTBE internal exposure level, the workers were divided into low- and high-exposed groups and found that the serum insulin level in the high-exposed group was significantly lower than that in the low-exposed group (p = 0.003) while fasting plasma glucose (FPG) level increased obviously in the high-exposed group compared to the low-exposed group (p = 0.001). Further analysis showed that MTBE exposure level was positively correlated with FPG level, but negatively correlated with serum insulin level, which suggested that the FPG level increase might be related to the decrease of serum insulin level induced by MTBE exposure. The results of further mediation effect analysis showed that changes in serum zinc levels played a major intermediary role in the process of insulin secretion inhibition and blood glucose elevation caused by MTBE exposure. In addition, a significant negative correlation was found between MTBE exposure and serum Zn level, which might play a strong mediating effect on the inhibition of insulin secretion induced by MTBE exposure. In conclusion, our study provided evidence that MTBE could inhibit insulin secretion and interfere with Zn metabolism in gas station workers for the first time, and found that Zn might play an important mediation effect during the process of inhibiting insulin secretion and interfering with glucose metabolism induced by MTBE exposure.

Prevalence and risk factors for subclinical hypothyroidism in older patients with major depressive disorder.

BACKGROUND: Subclinical hypothyroidism (SCH) is highly correlated with major depressive disorder (MDD). However, the prevalence and risk factors for SCH in older patients with MDD have rarely been reported in China. METHODS: This cross-sectional study included 266 older MDD patients with SCH was performed. Clinical and anthropometric, biochemical, and thyroid function data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Positive and Negative Syndrome Scale positive subscale, respectively. RESULTS: Among older patients with MDD, the prevalence of SCH was 64.7% (172/266). Compared to patients without SCH, older MDD patients with SCH had a longer disease course and higher TSH, A-TG, A-TPO, HDL-C, LDL-C, TC, FPG, and systolic pressure levels (all P ≤ 0.002). Furthermore, disease progression (OR 1.082, 95% CI 1.020-1.147, P = 0.009), A-TG (OR 1.005, 95% CI 1.001-1.009, P = 0.017), TC (OR 2.024, 95% CI 1.213-3.377, P = 0.007), FPG (OR 2.916, 95% CI 1.637-5.194, P < 0.001), systolic pressure (OR 1.053, 95% CI 1.008-1.100, P = 0.022) were independently associated with SCH, in older patients with MDD. CONCLUSIONS: Our findings suggest a high prevalence of SCH in older patients with MDD. Several demographic and clinical variables were independently associated with SCH in older patients with MDD.

Application of the Fpg-modified comet assay on three-spined stickleback in freshwater biomonitoring: toward a multi-biomarker approach of genotoxicity.

Aquatic species are exposed to a wide spectrum of substances, which can compromise their genomic integrity by inducing DNA damage or oxidative stress. Genotoxicity biomarkers as DNA strand breaks and chromosomal damages developed on sentinel species have already proved to be relevant in aquatic biomonitoring. However, these biomarkers do not reflect DNA oxidative lesions, i.e., the 8-oxodG, recognized as pre-mutagenic lesion if not or mis-repaired in human biomonitoring. The relevance to include the measure of these lesions by using the Fpg-modified comet assay on erythrocytes of the three-spined stickleback was investigated. An optimization step of the Fpg-modified comet assay considering enzyme buffer impact, Fpg concentration, and incubation time has been performed. Then, this measure was integrated in a battery of genotoxicity and cytotoxicity biomarkers (considering DNA strand breaks, DNA content variation, and cell apoptosis/necrosis and density) and applied in a freshwater monitoring program on six stations of the Artois Picardie watershed (3-week caging of control fish). These biomarkers allowed to discriminate the stations regarding the genotoxic potential of water bodies and specifically by the measure of oxidative DNA lesions, which seem to be a promising tool in environmental genotoxicity risk assessment.

Efficacy and Safety of a Fixed-Dose Combination of Vildagliptin and Pioglitazone in Indian Patients With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Comparative, Phase III Study.

Background Type 2 diabetes mellitus (T2DM) arises due to a range of pathological abnormalities, necessitating a combination therapy to achieve optimal glycemic control. Vildagliptin, an effective and selective DPP-4 inhibitor, and pioglitazone, an insulin sensitizer, offer distinct mechanisms of action. Hence, the integration of these medications represents a logical and justified therapeutic strategy Objective To compare the efficacy, safety, and tolerability of vildagliptin and pioglitazone 50 mg/15 mg fixed-dose combination (FDC) tablets with individual monotherapy vildagliptin 50 mg and pioglitazone 15 mg tablets in Indian T2DM patients who were inadequately controlled on metformin monotherapy. Methods This was a randomized, open-label, comparative, multicenter, phase III study involving 195 T2DM patients with inadequate glycemic control on metformin ≥ 1000 mg/day. Patients were randomly assigned in a 1:1:1 ratio to the test product group (n=65) (vildagliptin 50 mg + pioglitazone 15 mg FDC tablets), reference product group 1 (n=65) (vildagliptin 50 mg tablet), or reference product group 2 (n=65) (pioglitazone 15 mg tablet reference product). The primary endpoint was the mean change in HbA1c levels from baseline to end of the study visit (12 weeks (84 days ±2)). The secondary endpoints were the mean change in fasting plasma glucose (FPG) and 2-hr postprandial plasma glucose (2-hr PPG) levels. Safety parameters were assessed till the end of the study. Results A total of 178 patients completed the study. At 12 weeks, the mean HbA1c level in the test group reduced to 6.85 ± 1.27%, in the reference product 1 group to 7.56 ± 1.72%, and in the reference product 2 groups to 7.37 ± 1.59%. The mean change in Hb1Ac from baseline in the test group was statistically significant compared to the reference groups (p=0.037). Similarly, the mean changes in the FPG and 2hr-PPG with the test product were statistically significant compared to reference products (p=0.041). The adverse events were comparable across all the treatment groups. Conclusion In Indian T2DM patients inadequately controlled on a daily maximum dose of metformin, treatment with vildagliptin and pioglitazone FDC showed better glycemic control than either vildagliptin or pioglitazone along with a good tolerability profile.

The dangerous link between coal dust exposure and DNA damage: unraveling the role of some of the chemical agents and oxidative stress.

Exposure to coal mining dust poses a substantial health hazard to individuals due to the complex mixture of components released during the extraction process. This study aimed to assess the oxidative potential of residual coal mining dust on human lymphocyte DNA and telomeres and to perform a chemical characterization of coal dust and urine samples. The study included 150 individuals exposed to coal dust for over ten years, along with 120 control individuals. The results revealed significantly higher levels of DNA damage in the exposed group, as indicated by the standard comet assay, and oxidative damage, as determined by the FPG-modified comet assay. Moreover, the exposed individuals exhibited significantly shorter telomeres compared to the control group, and a significant correlation was found between telomere length and oxidative DNA damage. Using the PIXE method on urine samples, significantly higher concentrations of sodium (Na), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), iron (Fe), zinc (Zn), and bromine (Br) were observed in the exposed group compared to the control group. Furthermore, men showed shorter telomeres, greater DNA damage, and higher concentrations of nickel (Ni), calcium (Ca), and chromium (Cr) compared to exposed women. Additionally, the study characterized the particles released into the environment through GC-MS analysis, identifying several compounds, including polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene, naphthalene, anthracene, 7H-benzo[c]fluorene, phenanthrene, pyrene, benz[a]anthracene, chrysene, and some alkyl derivatives. These findings underscore the significant health risks associated with exposure to coal mining dust, emphasizing the importance of further research and the implementation of regulatory measures to safeguard the health of individuals in affected populations.

Bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes in adults: A 24-week, randomized, double-blind, placebo-controlled trial.

AIM: To evaluate the relative safety and effectiveness of bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes mellitus. METHODS: In total, 317 participants were randomized to receive bexagliflozin or placebo plus metformin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24, with secondary endpoints for systolic blood pressure (SBP), fasting plasma glucose and weight loss. An open label arm enrolled participants with HbA1c >10.5% and was analysed separately. RESULTS: The mean change in HbA1c was -1.09% (95% CI -1.24%, -0.94%) in the bexagliflozin arm and -0.56% (-0.71%, -0.41%) in the placebo arm, a difference of -0.53% (-0.74%, -0.32%; p < .0001). Excluding observations after rescue medication, the intergroup difference was -0.70% (-0.92, -0.48; p < .0001). The open label group change in HbA1c was -2.82% (-3.23%, -2.41%). Placebo-adjusted changes from baseline SBP, fasting plasma glucose and body mass were -7.07 mmHg (-9.83, -4.32; p < .0001), -1.35 mmol/L (-1.83, -0.86; p < .0001) and -2.51 kg (-3.45, -1.57; p < .0001). Adverse events affected 42.4% and 47.2% of subjects in the bexagliflozin and placebo arms, respectively; fewer subjects in the bexagliflozin arm experienced serious adverse events. CONCLUSIONS: Bexagliflozin produced clinically meaningful improvement in glycaemic control, estimated glomerular filtration rate and SBP when added to metformin in a population of adults with diabetes.

Unexpected finding of a rare pathogenic germline BRCA1 variant in an intrahepatic cholangiocarcinoma using the Oncomine Focus DNA assay: clinical and diagnostic implications.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor arising from the epithelial cells of the bile ducts and is the second most common liver cancer after hepatocellular carcinoma. Recently, our Institution launched a Comprehensive Genomic Profiling (CGP) program (named FPG500 program), set up to provide a complete molecular characterization through the TruSight Oncology 500 High Throughput (TSO500HT) solution and samples that do not reach pre-set sample quantity and/or quality thresholds required for TSO500HT, are addressed to Oncomine Focus DNA Assay (OFA) and the Archer's FusionPlex Lung Panel (AFL). METHODS AND RESULTS: Here we report the case of a patient with iCCA enrolled in the FPG500 program and screened by the orthogonal workflow (OFA/AFL). Although BRCA1 is not among the genes declared in the OFA panel, we unexpectedly detected a pathogenic variant in this gene (c.5278-2del, rs878853285). CONCLUSIONS: This case highlights the diagnostic capabilities of CGP, now widely used in both clinical practice and academic setting. The incidental involvement of BRCA1 focuses attention on the role of BRCA genes in biliary tract cancers. Finally, as an orthogonal test confirmed the germline origin of BRCA1 c.5278-2del variant, the germline implications of CGP need to be considered.

The levels and trends of diabetes prevalence at national and sub-national levels in Iran (1990 - 2016).

Background: The increasing trends in Diabetes prevalence and its attributed burden emphasized as an important issue that needs serious and urgent attention, all over the word. We estimated the mean Fasting Plasma Glucose (FPG) and the prevalence of Diabetes in aged 25 years or older Iranian adults, by sex, age, province, and year through the time period of 1990 to 2016. Methods: In order to access the most comprehensive relevant data at the same time the systematic data searched added to the data of 5 national surveys and 7 sub-national population based investigations. Two round of modeling, including the Age-Spatio-Temporal and Gaussian Process Regression were used for estimation of mean FPG trend and uncertainties. To estimate Diabetes estimations in target groups, a crosswalk model was applies to the FPG estimates. The model reiterated separately for women and men. All of estimations standardized based on the Iran national census population of 2016 by year, age groups and sexes at national and sub-national levels. Results: In 2016, the number of the diabetic population was 4.43 (3.93-4.99) million (2.38 million women). Between 1990 and 2016, the age-standardized mean of FPG increased from 84.69 mg/dl (79.8-89.8) to 100.5 mg/dl (97.9-103.3) in women and from 82.7 mg/dl (78.3-87.5) to 98.8 mg/dl (96.2-101.4) in men. Simultaneously, with considerable difference, the Diabetes prevalence, has increased from 6.1% (4.7-7.8) to 9.8% (8.7-11.1) in women and from 5.0% 18 (3.8-6.3) to 8.1% (7.2-9.2) in men (75% attributed to population growth). Considering the geographical patterns, the greatest increment in the prevalence of Diabetes detected in the northwestern and the central provinces. Conclusion: Significant increasing trends of Diabetes led to alarming threat, which can make the strategies and goals of our prevention programs out of control. We should plan for more effective communicative interventions for prevention and management of Diabetes, to be designed, implemented and monitored based on the updated scientific evidence. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01197-2.

Effect of endodontic treatment on clinical outcome in type 2 diabetic patients with apical periodontitis.

Background: Previous research has demonstrated that poor controlled diabetic showed higher prevalence of AP compared to well-controlled patients and endodontic treatment may improve metabolic control of patients with diabetes. The purpose of this trial was to clinically assess the effects of endodontic treatment on glycemic control in patients with type 2 diabetes mellitus (T2DM) and apical periodontitis (AP). Study design: For present trial, AP + T2DM with patients insulin injection (Group1, G1,n = 65), AP + T2DM patients with hypoglycaemic agents (Group2, G2, n = 82), and AP patients without DM (Group3, G3, n = 86) were enrolled. After demographic characteristics and clinical examination were achieved, root canal treatment (RCT) was performed for each patient. Subjects were followed up at 2-week, 3- and 6-month. At each visit, blood samples were taken and clinical laboratory studies were performed. At 6-month follow-up, Periapical Index (PAI) score was used to assess the periapical status. Results: A total of 237 subjects who met the including criteria were allocated in three groups and 223 subjects (94.1%) completed the treatments and the follow-up assessments. After treatment, taking PAI into consideration, both groups showed significant improvement of AP in each group (P < 0.05). Patients in G3 had a continued significant lower concentration of fasting plasma glucose (FPG) levels at follow-up (P < 0.05). A continued reduction of hemoglobin glycation (HbA1c) was observed in most of time points (P < 0.05). Throughout the trial, there are also significant changes in inflammatory factors in short-term. Conclusion: Endodontic therapy improved AP healing, glycemic control and systemic inflammation in patients with T2DM and/or AP in each group. However, a continued reduction in inflammatory factors and decreasing of HbA1c in short-term could not be observed in this trial.

Comparison of weight change between face-to-face and digital delivery of the English National Health service diabetes prevention programme: An exploratory non-inferiority study with imputation of plausible weight outcomes.

Worldwide evidence suggests face-to-face diabetes prevention programmes are effective in preventing and delaying the onset of type 2 diabetes by encouraging behaviour change towards weight loss, healthy eating, and increased exercise. There is an absence of evidence on whether digital delivery is as effective as face-to-face. During 2017-18 patients in England were offered the National Health Service Diabetes Prevention Programme as group-based face-to-face delivery, digital delivery ('digital-only') or a choice between digital and face-to-face ('digital-choice'). The contemporaneous delivery allowed for a robust non-inferiority study, comparing face-to-face with digital only and digital choice cohorts. Changes in weight at 6 months were missing for around half of participants. Here we take a novel approach, estimating the average effect in all 65,741 individuals who enrolled in the programme, by making a range of plausible assumptions about weight change in individuals who did not provide outcome data. The benefit of this approach is that it includes everyone who enrolled in the programme, not restricted to those who completed. We analysed the data using multiple linear regression models. Under all scenarios explored, enrolment in the digital diabetes prevention programme was associated with clinically significant reductions in weight which were at least equivalent to weight loss in the face-to-face programme. Digital services can be just as effective as face-to-face in delivering a population-based approach to the prevention of type 2 diabetes. Imputation of plausible outcomes is a feasible methodological approach, suitable for analysis of routine data in settings where outcomes are missing for non-attenders.

Assay conditions for estimating differences in base excision repair activity with Fpg-modified comet assay.

DNA repair is an essential agent in cancer development, progression, prognosis, and response to therapy. We have adapted a cellular repair assay based on the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay to assess DNA repair kinetics. The removal of oxidized nucleobases over time (0-480 min) was analyzed in peripheral blood mononuclear cells (PBMCs) and 8 cell lines. DNA damage was induced by exposure to either Ro19-8022 plus visible light or potassium bromate (KBrO3). The initial amount of damage induced by Ro 19-8022 plus light varied between cell lines, and this was apparently associated with the rate of repair. However, the amount of DNA damage induced by KBrO3 varied less between cell types, so we used this agent to study the kinetics of DNA repair. We found an early phase of ca. 60 min with fast removal of Fpg-sensitive sites, followed by slower removal over the following 7 h. In conclusion, adjusting the initial damage at T0 to an equal level can be achieved by the use of KBrO3, which allows for accurate analysis of subsequent cellular DNA repair kinetics in the first hour after exposure.

Association between fasting plasma glucose variability and maternal and infant outcomes in patients with hyperglycemia during pregnancy: a retrospective cohort study.

Background: Blood glucose variability (GV) is believed to be closely related to the occurrence of adverse obstetric outcomes. However, few studies have investigated how the change in fasting plasma glucose (FPG) influenced on the adverse obstetric outcomes. This study mainly evaluated the relationship between FPG coefficient of variation (FPG-CV) and adverse outcomes in patients with gestational hyperglycemia and determine the ideal FPG-CV threshold for predicting maternal and infant outcomes. Methods: We retrospective analyzed the data of 608 pregnant hyperglycemic patients in the Obstetrics Department of Shengjing Hospital Affiliated to China Medical University between June 2019 and December 2021 and followed up inpatients through the Hospital Information System (HIS). We collected the venous FPG from 24-28 weeks of pregnancy to delivery. Maternal and infant outcomes were based on the latest definitions. The chi-square test and logistic regression analysis were performed to evaluate the correlation between FPG-CV and adverse outcomes. Two multivariate binary logistic regression models were used to adjust for confounding factors. Stratified analysis was performed according to hemoglobin A1c (HbA1c) levels (<5.9% and ≥5.9%) and insulin injection (not used and used) in the third trimester of pregnancy. The receiver operating characteristic (ROC) curve was used to evaluate the prediction of FPG-CV on adverse outcomes. Results: All patients were divided into four groups based on the quartile of FPG-CV. The proportion of FPG-SD and insulin injections differed among the groups (P<0.05). Among the outcomes, the highest incidence rate was 26.3% for large for gestational age (LGA), 8.7% for premature delivery. FPG-CV remains independently associated with low birth weight [odds ratio (OR) =1.086, P=0.007], preterm birth (OR =1.069, P=0.012), and preeclampsia (OR =1.180, P<0.001). FPG-CV can predict preeclampsia, with an area under the curve (AUC) of 0.725. Conclusions: Our results suggest that patients with gestational hyperglycemia should undergo routine FPG monitoring from diagnosis to delivery. Also, the impact of blood glucose fluctuations on adverse outcomes should be considered in the clinical treatment. The rational application of hypoglycemic treatment can stabilize blood glucose levels, however, the effects of different regimens on GV and outcomes should be studied further.

Comparison of diagnostic accuracy for diabetes diagnosis: A systematic review and network meta-analysis.

Aim: Fasting Plasma Glucose (FPG) and Hemoglobin A1c (HbA1c) are used as diagnostic tests for diagnosing diabetes mellitus, but it is unclear which test has the best diagnostic accuracy. This systematic review and network meta-analysis aimed to estimate the diagnostic accuracy of HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and the combination of HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl (HbA1c| FPG), compared with Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dl for diagnosis diabetes. Materials and methods: We performed a comprehensive search in PubMed, Embase, Cochrane Library, and Scopus from inception to September 24th, 2021. Inclusion criteria were any study design comparing HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl with OGTT ≥ 200 mg/dl as the reference test. Data were independently extracted, risk of bias was assessed using QUADAS-2 by two reviewers. Network meta-analysis was done using a bivariate regression model using the Bayesian framework. The relative ranking of all tests was also assessed. Results: Out of 5,026 studies, 73 were included. The sensitivities of HbA1c, FPG, and HbA1c| FPG were 0.51 [95% Credible Interval (CrI): 0.43, 0.58], 0.49 (95% CrI: 0.43, 0.55), and 0.64 (95% CrI: 0.51, 0.75), while the specificities were 0.96 (95% CrI: 0.94, 0.97), 0.98 (95% CrI: 0.97, 0.98), and 0.95 (95% CrI: 0.88, 0.98), respectively. The corresponding positive likelihood ratios (LR) were 13.36 (95% CrI: 8.91, 20.72), 21.94 (95% CrI: 15.04, 31.88), and 11.78 (95% CrI: 5.48, 26.56). HbA1c| FPG is superior based on sensitivity, whereas FPG is ranked best based on specificity and positive LR. Conclusion: Our findings suggest that FPG ≥ 126 mg/dl should be recommended as the best diagnostic test for diabetes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021282856.

Toxicological evaluation of polycrystalline wools in human lung cells.

Aim: Polycrystalline wools (PCW) are included with Refractory ceramic fibers (RCF) in the alumino-silicates family of High Temperature Insulation Wools (HTIW). IARC includes PCW in the ceramic fibers group and considers them as possible human carcinogens (GROUP 2B). Since PCW toxicity is not yet clear, our aim was to evaluate their toxic and inflammatory effects and to compare them with the known RCF effects.Method: We exposed human bronchial (BEAS-2B) and alveolar (A549) cells to 2-100 µg/mL (2.4 × 103-1.2 × 105 fibers/mL; 2.51 × 103-1.26 × 105 fibers/cm2 of PCW and 7.4 × 103-3.7 × 105 fibers/mL; 7.75 × 103-3.87 × 105 fibers/cm2 of RCF) of the tested fibers to evaluate potential viability reduction, apoptosis, membrane damage, direct/oxidative DNA-damage, cytokine release.Results: In A549, PCW did not induce cytotoxicity and apoptosis but they induced significant dose-dependent DNA-damage, although lower than RCF; only RCF induced oxidative effects. PCW also induced an increase in IL-6 release at 100 µg/mL (1.2 × 105 fibers/mL; 1.26 × 105 fibers/cm2). In BEAS-2B, PCW did not induce cell-viability reduction RCF induced a dose-dependent cell-viability decrease. Both fibers show a dose-dependent increase of apoptosis. In BEAS-2B, PCW also induced dose-dependent DNA-damage, although lower than RCF, and slight oxidative effects similar to RCF. PCW also induced an increase of IL-6 release; RCF induced a decrease of IL-8. Summarizing, PCW induce direct-oxidative DNA-damage although to a lower extent than RCF observed by both mass-based and fiber number-based analysis.Conclusion: For the first time, the study shows the potential toxicity of PCW, usually considered safe, and suggests to perform further in vitro studies, also on other cell types, to confirm these findings.

Aluminium(III) Oxide-The Silent Killer of Bacteria.

In this article, we describe the antimicrobial properties of pristine anodised aluminium oxide matrices-the material many consider biologically inert. During a typical anodisation process, chromium and chlorine compounds are used for electropolishing and the removal of the first-step aluminium oxide. Matrices without the use of those harmful compounds were also fabricated and tested for comparison. The antibacterial tests were conducted on four strains of Escherichia coli: K12, R2, R3 and R4. The properties of the matrices were also compared to the three types of antibiotics: ciprofloxacin, bleomycin and cloxacillin using the Minimal Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than the aforementioned antibiotics. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA.